Pathway for the Synthesis of Fatty Acids in Mammalian Tissues

Lin, Chu Yuan; Kumar, Soma

doi:10.1016/s0021-9258(19)45745-1

Cited by 50 publications

(5 citation statements)

References 9 publications

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“…1 , C and D and 3 , M – O ). Importantly, (iso)butyryl-CoA can be an intermediate in FAS downstream of AcCoA ( 52 ). Even though the acute time points and the nutrient-depleted conditions (acetate depletion is nonlipogenic in Acly −/− MEFs ( 27 )) did not allow us to directly examine acetate carbon incorporation into lipogenesis, our data suggest that deacetylation may be used for anabolic pathways such as FAS.…”

Section: Discussionmentioning

confidence: 99%

Dynamic protein deacetylation is a limited carbon source for acetyl-CoA–dependent metabolism

Soaita

Megill

Kantner

et al. 2023

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Dynamic protein deacetylation is a limited carbon source for acetyl-CoA–dependent metabolism

Soaita

Megill

Kantner

et al. 2023

Journal of Biological Chemistry

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“…Decreases in milk C4:0 yield are not common, because this FA has a low melting point (−5.3°C), helping to maintain milk fat fluidity at body temperature (Barbano and Sherbon, 1980;Scrimgeour and Harwood, 2007). Also, the pathway to generate C4:0 involves the use of a more efficient primer (butyryl-CoA) independent from malonyl-CoA, which spares ATP and NADPH (Palmquist et al, 1969;Lin and Kumar, 1972;Smith et al, 1974).…”

Section: Discussionmentioning

confidence: 99%

Effects of calcium salts of palm fatty acids on nutrient digestibility and production responses of lactating dairy cows: A meta-analysis and meta-regression

Neto

Souza

Lock

2021

Journal of Dairy Science

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Our primary objective was to perform a meta-analysis and meta-regression to evaluate the effects of diets supplemented with calcium salts of palm fatty acids (CSPF) compared with nonfat supplemented control diets (CON) on nutrient digestibility and production responses of lactating dairy cows. Our secondary objective was to perform a meta-analysis to evaluate whether experimental design affects production responses to supplemental CSPF. The data set was formed from 33 peer-reviewed publications with CSPF supplemented at ≤3% diet dry matter. We analyzed the interaction between experimental design (continuous vs. change-over) and treatments (CON vs. CSPF) to evaluate whether experimental design affects responses to CSPF (Meta.1). Regardless of experimental design, we evaluated the effects of CSPF compared with CON on nutrient digestibility and production responses of lactating dairy cows by meta-analysis (Meta.2) and meta-regression (Meta.3) approaches. In Meta.1, there was no interaction between treatments and experimental design for any variable. In Meta.2, compared with CON, CSPF reduced dry matter intake [DMI, 0.56 ± 0.21 kg/d (±SE)] and milk protein content (0.05 ± 0.02 g/100 g), increased neutral detergent fiber (NDF) digestibility (1.60 ± 0.57 percentage units), the yields of milk (1.53 ± 0.56 kg/d), milk fat (0.04 ± 0.02 kg/d), and 3.5% fat corrected milk (FCM, 1.28 ± 0.60 kg/d), and improved feed efficiency [energy corrected milk (ECM)/DMI, 0.08 kg/kg ± 0.03]. There was no effect of treatment for milk protein yield, milk fat content, body weight, body weight change, or body condition score. Compared with CON, CSPF reduced the yield of de novo milk fatty acids (FA) and increased the yields of mixed and preformed milk FA. In Meta.3, we observed that each 1-percentage-unit increase of CSPF in diet dry matter reduced DMI, increased NDF digestibility, tended to increase FA digestibility, increased the yields of milk, milk fat, and 3.5% FCM, reduced the content of milk protein, reduced the yield of de novo milk FA, and increased the yields of mixed and preformed milk FA. In conclusion, our results indicate no reason for the restrictive use of change-over designs in CSPF supplementation studies or meta-analysis. Feeding CSPF increased NDF digestibility, tended to increase FA digestibility, and increased the yields of milk, milk fat, and 3.5% FCM. Additionally, CSPF increased milk fat yield by increasing the yields of mixed and preformed milk FA.

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“…We identify (iso)butyryl-CoA as downstream of acetyl-CoA in our system, since labeling occurs rapidly upon 13 C-acetate introduction but is slightly slower than acetyl-CoA (Fig 1C,D), consistent with pattern observed in other downstream pathways [40]. Furthermore, ACSS2 inhibition reduces carbon contribution of protein-derived acetate to (iso)butyryl-CoA (S4 Fig) . Importantly, (iso)butyryl-CoA can be an intermediate in the fatty acid synthesis pathway downstream of acetyl-CoA [51]. Our data therefore suggest the intriguing possibility that protein-derived acetate can be used for anabolic pathways such as fatty acid synthesis.…”

Section: Protein Deacetylation Can Potentially Support Acetyl-coadepe...mentioning

confidence: 76%

“…Furthermore, ACSS2 inhibition reduces carbon contribution of protein-derived acetate to (iso)butyryl-CoA (S4 Fig). Importantly, (iso)butyryl-CoA can be an intermediate in the fatty acid synthesis pathway downstream of acetyl-CoA [51]. Our data therefore suggest the intriguing possibility that protein-derived acetate can be used for anabolic pathways such as fatty acid synthesis.…”

Section: Discussionmentioning

confidence: 95%

Dynamic protein deacetylation is a limited carbon source for acetyl-CoA-dependent metabolism

Soaita

Megill

Kantner

et al. 2022

Preprint

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The ability of cells to store and rapidly mobilize energy reserves in response to nutrient availability is essential for survival. Breakdown of carbon stores produces acetyl-coenzyme-A (acetyl-CoA), which fuels various metabolic pathways and is also the acyl donor for protein lysine acetylation. Notably, histone acetylation is sensitive to acetyl-CoA availability and nutrient replete conditions induce a substantial accumulation of acetylation on histones. Deacetylation releases acetate, which can be recycled to acetyl-CoA, suggesting that deacetylation could be mobilized as an acetyl-CoA source to feed downstream metabolic processes under nutrient depletion. While the notion of histones as a metabolic reservoir has been frequently proposed, experimental evidence has been lacking. Therefore, to test this concept directly, we developed an experimental system to trace deacetylation-derived acetate and its incorporation into acetyl-CoA, using13C2-acetate in ATP citrate lyase-deficient fibroblasts (Acly-/- MEFs), which are primarily dependent on acetate for protein acetylation. We find that dynamic protein deacetylation in Acly-/- MEFs contributes carbons to acetyl-CoA and proximal downstream metabolites. However, there is no significant effect on acyl-CoA pool sizes, and even at maximal acetylation, deacetylation transiently supplies approximately 9% of cellular acetyl-CoA. Together, our data reveal that although protein acetylation is dynamic and sensitive to nutrient availability, its potential for maintaining cellular acetyl-CoA-dependent metabolic pathways is limited compared to cellular demand.

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Pathway for the Synthesis of Fatty Acids in Mammalian Tissues

Cited by 50 publications

References 9 publications

Dynamic protein deacetylation is a limited carbon source for acetyl-CoA–dependent metabolism

Dynamic protein deacetylation is a limited carbon source for acetyl-CoA–dependent metabolism

Effects of calcium salts of palm fatty acids on nutrient digestibility and production responses of lactating dairy cows: A meta-analysis and meta-regression

Dynamic protein deacetylation is a limited carbon source for acetyl-CoA-dependent metabolism

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